EP1041960B1 - Use of polyanionic and polyanionically-derivatised natural polysaccharides for inhibiting alkaline phosphatase - Google Patents
Use of polyanionic and polyanionically-derivatised natural polysaccharides for inhibiting alkaline phosphatase Download PDFInfo
- Publication number
- EP1041960B1 EP1041960B1 EP98965242A EP98965242A EP1041960B1 EP 1041960 B1 EP1041960 B1 EP 1041960B1 EP 98965242 A EP98965242 A EP 98965242A EP 98965242 A EP98965242 A EP 98965242A EP 1041960 B1 EP1041960 B1 EP 1041960B1
- Authority
- EP
- European Patent Office
- Prior art keywords
- derivatised
- polyanionic
- polyanionically
- use according
- formula
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 150000004676 glycans Chemical class 0.000 title claims description 31
- 229920001282 polysaccharide Polymers 0.000 title claims description 31
- 239000005017 polysaccharide Substances 0.000 title claims description 31
- 102000002260 Alkaline Phosphatase Human genes 0.000 title claims description 17
- 108020004774 Alkaline Phosphatase Proteins 0.000 title claims description 17
- 230000002401 inhibitory effect Effects 0.000 title claims description 9
- 239000000203 mixture Substances 0.000 claims description 33
- 229920001661 Chitosan Polymers 0.000 claims description 20
- 150000001875 compounds Chemical class 0.000 claims description 17
- 244000005700 microbiome Species 0.000 claims description 17
- 230000001580 bacterial effect Effects 0.000 claims description 8
- 229920002498 Beta-glucan Polymers 0.000 claims description 7
- 238000002360 preparation method Methods 0.000 claims description 7
- 239000007787 solid Substances 0.000 claims description 7
- 229920000388 Polyphosphate Polymers 0.000 claims description 6
- 239000001205 polyphosphate Substances 0.000 claims description 6
- 235000011176 polyphosphates Nutrition 0.000 claims description 6
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 claims description 5
- 229920001503 Glucan Polymers 0.000 claims description 4
- 235000011180 diphosphates Nutrition 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 235000019832 sodium triphosphate Nutrition 0.000 claims description 4
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical group OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 claims description 3
- 239000013543 active substance Substances 0.000 claims description 3
- 229910052783 alkali metal Inorganic materials 0.000 claims description 3
- 229940005740 hexametaphosphate Drugs 0.000 claims description 3
- 230000002265 prevention Effects 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 claims description 3
- UNXRWKVEANCORM-UHFFFAOYSA-I triphosphate(5-) Chemical compound [O-]P([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O UNXRWKVEANCORM-UHFFFAOYSA-I 0.000 claims description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims description 2
- 229920002101 Chitin Polymers 0.000 claims description 2
- 229920002307 Dextran Polymers 0.000 claims description 2
- 229920002683 Glycosaminoglycan Polymers 0.000 claims description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- 239000003513 alkali Substances 0.000 claims description 2
- 150000001340 alkali metals Chemical class 0.000 claims description 2
- 230000000845 anti-microbial effect Effects 0.000 claims description 2
- 125000001246 bromo group Chemical group Br* 0.000 claims description 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims description 2
- 150000002500 ions Chemical class 0.000 claims description 2
- YACKEPLHDIMKIO-UHFFFAOYSA-N methylphosphonic acid Chemical group CP(O)(O)=O YACKEPLHDIMKIO-UHFFFAOYSA-N 0.000 claims description 2
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 claims description 2
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- 239000003814 drug Substances 0.000 claims 2
- FYGDTMLNYKFZSV-URKRLVJHSA-N (2s,3r,4s,5s,6r)-2-[(2r,4r,5r,6s)-4,5-dihydroxy-2-(hydroxymethyl)-6-[(2r,4r,5r,6s)-4,5,6-trihydroxy-2-(hydroxymethyl)oxan-3-yl]oxyoxan-3-yl]oxy-6-(hydroxymethyl)oxane-3,4,5-triol Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1[C@@H](CO)O[C@@H](OC2[C@H](O[C@H](O)[C@H](O)[C@H]2O)CO)[C@H](O)[C@H]1O FYGDTMLNYKFZSV-URKRLVJHSA-N 0.000 claims 1
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- FQENQNTWSFEDLI-UHFFFAOYSA-J sodium diphosphate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]P([O-])(=O)OP([O-])([O-])=O FQENQNTWSFEDLI-UHFFFAOYSA-J 0.000 description 4
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- CGMRCMMOCQYHAD-UHFFFAOYSA-J dicalcium hydroxide phosphate Chemical compound [OH-].[Ca++].[Ca++].[O-]P([O-])([O-])=O CGMRCMMOCQYHAD-UHFFFAOYSA-J 0.000 description 2
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 2
- 229910000396 dipotassium phosphate Inorganic materials 0.000 description 2
- 235000019820 disodium diphosphate Nutrition 0.000 description 2
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- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 1
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- XZKIHKMTEMTJQX-UHFFFAOYSA-N 4-Nitrophenyl Phosphate Chemical compound OP(O)(=O)OC1=CC=C([N+]([O-])=O)C=C1 XZKIHKMTEMTJQX-UHFFFAOYSA-N 0.000 description 1
- BTJIUGUIPKRLHP-UHFFFAOYSA-N 4-nitrophenol Chemical compound OC1=CC=C([N+]([O-])=O)C=C1 BTJIUGUIPKRLHP-UHFFFAOYSA-N 0.000 description 1
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- GHXZTYHSJHQHIJ-UHFFFAOYSA-N Chlorhexidine Chemical compound C=1C=C(Cl)C=CC=1NC(N)=NC(N)=NCCCCCCN=C(N)N=C(N)NC1=CC=C(Cl)C=C1 GHXZTYHSJHQHIJ-UHFFFAOYSA-N 0.000 description 1
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- HMEKVHWROSNWPD-UHFFFAOYSA-N Erioglaucine A Chemical compound [NH4+].[NH4+].C=1C=C(C(=C2C=CC(C=C2)=[N+](CC)CC=2C=C(C=CC=2)S([O-])(=O)=O)C=2C(=CC=CC=2)S([O-])(=O)=O)C=CC=1N(CC)CC1=CC=CC(S([O-])(=O)=O)=C1 HMEKVHWROSNWPD-UHFFFAOYSA-N 0.000 description 1
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- 150000003863 ammonium salts Chemical class 0.000 description 1
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- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
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- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
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- 229920001059 synthetic polymer Polymers 0.000 description 1
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- RYCLIXPGLDDLTM-UHFFFAOYSA-J tetrapotassium;phosphonato phosphate Chemical compound [K+].[K+].[K+].[K+].[O-]P([O-])(=O)OP([O-])([O-])=O RYCLIXPGLDDLTM-UHFFFAOYSA-J 0.000 description 1
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- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical class [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q11/00—Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/34—Alcohols
- A61K8/347—Phenols
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
- A61K8/73—Polysaccharides
- A61K8/736—Chitin; Chitosan; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/74—Biological properties of particular ingredients
- A61K2800/78—Enzyme modulators, e.g. Enzyme agonists
- A61K2800/782—Enzyme inhibitors; Enzyme antagonists
Definitions
- the present invention relates to the use of polyanionic and polyanionically-derivatised natural polysaccharides or non-derivatised natural polysaccharides for inhibiting alkaline phosphatase as well as to oral preparations comprising these compounds.
- Tartar is understood to mean deposits which form at the margin of the gum on the surface of the teeth. These deposits consist both of inorganic material - in particular calcium hydrogenoxylapatite (HAP) - and of organic components, such as epithelial cells, food particles, saliva sediments and different kinds of microorganisms.
- HAP calcium hydrogenoxylapatite
- This whitish, yellowish or often blotchy tartar is undesirable not only because of its appearance but mainly because it gives constant occasion to irritations of the oral mucosa and to the development of gingivitis and diseases of the theeth and teeth socket. Such deposits are prevented on the one hand by daily dental care and by the concomitant microdecalcification. In addition, it is usually necessary to have the dentist remove tartar mechanically from time to time.
- Safe and effective agents for inhibiting tartar formation are, for example, the water-soluble, molecularly dehydrated polyphosphates known as sequestrants and chelating agents, such as hexametaphosphates, tripolyphosphates and pyrophosphates, which prevent the formation of HAP (cf. US-A-4,515,722).
- sequestrants and chelating agents such as hexametaphosphates, tripolyphosphates and pyrophosphates, which prevent the formation of HAP (cf. US-A-4,515,722).
- the effect of these compounds is significantly reduced by the saliva enzymes present in the mouth and throat area, such phosphate compounds being hydrolysed in particular by alkaline phosphatases.
- US-A-5,094,844 proposes to reduce the deactivating effect of alkaline phosphatase, i.e. the hydrolysis of the linear molecularly dehydrated polyphosphates, by addition of an anionic polyvinyl phosphonate.
- EP-A-0803243 describes an oral composition comprising 0-2% of carageenan, 0-10% of pyrophosphate salts as well as Triclosan (TM).
- TM Triclosan
- WO 97 48372 A discloses a toothpaste containing carageenan and tetrasodium pyrophosphate.
- this invention relates to the use of polyanionic and polyanionically-derivatised natural polysaccharides or non-derivatised natural polysaccharides for inhibiting alkaline phosphatase.
- this invention relates to the use of polyanionic and polyanionically-derivatised natural polysaccharides for inhibiting alkaline phosphatase.
- polyanionic and polyanionically-derivatised natural polysaccharides used are preferably
- Polyanionically-derivatised natural polysaccharides are preferably those compounds which contain phosphate groups, phosphonate groups or methylphosphonate groups, such as
- the polyanionic and polyanionically-derivatised natural polysaccharides used according to this invention preferably have a molecular weight of > 5000.
- Preferred phosphochitosans are in particular phosphonomethylated chitosans corresponding to formula wherein
- the non-derivatised natural polysaccharides used according to this invention are preferably glucans. It is preferred to use ⁇ -1,3-glucans corresponding to formula wherein
- the polyanionic and polyanionically-derivatised natural polysaccharides and the non-derivatised natural polysaccharides used according to this invention inhibit the adhesion of microorganisms, in particular of anaerobic microorganisms, on solid surfaces, especially in holes, interspaces, deposits, pockets in the mouth and throat area, and that they thus reduce or inhibit the negative effects of these germs, in particular the formation of plaque and calculus, or dental decay, bad breath (malodor) and deposits on dentures.
- These compounds can also detach the microorganisms from solid surfaces (desorption).
- the buffer capacity of the phosphonomethylated chitosan stabilises the intrabuccal pH and prevents hyperacidity and hence tooth decay.
- the phosphonomethylated chitosans of formulae (1) and (2) and the glucans of formula (3) are compounds which are biocompatible and completely bio-degradable.
- this invention relates to an oral composition, which comprises .
- Component (a) in the novel oral composition is preferably hexametaphosphate, tripolyphosphate, pyrophosphate or mixtures of these compounds.
- the polyphosphates can comprise, for example, 2 to 120 phosphorus atoms and are used in the novel oral composition in amounts from 0.01 to 10 % by weight, preferably from 2 to 5 % by weight, based on the total weight of the composition.
- Pyrophosphate is preferably used as a mixture of tetrapotassium pyrophosphate and tetrasodium pyrophosphate.
- the novel composition may also contain antimicrobial active substances, for example phenol derivatives, diphenyl compounds, benzyl alcohols, chlorohexidine, C 12 -C 14 alkylbetaine, C 8 -C 18 fatty acid amidoalkylbetaine, amphoteric surfactants, trihalocarbanilides, quaternary ammonium salts and, very particularly, 2-hydroxydiphenyl ethers of formula wherein
- the novel oral composition can also comprise compounds releasing fluoride ions which are effective against caries formation, for example inorganic fluoride salts, such as sodium fluoride, potassium fluoride, ammonium fluoride or calcium fluoride, or organic fluoride salts, for example amine fluorides which are known under the tradename Olafluor. These compounds may be present in the novel composition in amounts of 0.005 to 3 % by weight, depending on solubility and kind of composition.
- inorganic fluoride salts such as sodium fluoride, potassium fluoride, ammonium fluoride or calcium fluoride
- organic fluoride salts for example amine fluorides which are known under the tradename Olafluor.
- the novel oral composition is preferably liquid, for example in the form of a mouth wash or mouth rinse, the composition preferably being a 1:1 to 20:1, preferably a 2:1 to 10:1, mixture of water and alcohol.
- the pH of the novel oral composition is 4.5 to 9, preferably 5.5 to 8.
- the novel oral composition can also be in solid or pasty form, for example in the form of tooth powder, tooth tablet, toothpaste, tooth gel or tooth cream.
- a solid or pasty composition usually comprises an orally acceptable, water-insoluble polishing material.
- polishing materials are water-insoluble metaphosphates, tricalcium phosphates, dehydrated dicalcium phosphates, calcium pyrophosphates, aluminium silicates, zirconium silicates, bentonite, or mixtures of these compounds.
- the polishing material is usually present in the solid or pasty composition in amounts of 10 to 90 % by weight, preferably of 10 to 75 % by weight.
- the novel oral composition can also contain further materials, for example whitening agents, preservatives, silicones, chlorophyll compounds, other agents for the prevention of bacterial plaque, urea, diammonium phosphates, and mixtures thereof.
- These adjuvants are present in the novel compositions in such concentrations that the positive properties of the composition are not affected.
- novel composition may contain flavouring and sweetening agents, for example peppermint oil, eucalyptus, marjoram, cinnamon, saccharin and the like.
- flavouring and sweetening agents for example peppermint oil, eucalyptus, marjoram, cinnamon, saccharin and the like.
- the novel oral composition can be incorporated into lozenges, chewing gum or other products, for example by being stirred into a warm gum material or by coating the exterior surfaces of a chewing gum.
- alkaline phosphatase The activity of alkaline phosphatase is measured using the kinetic colour test for clinical-chemical analytical systems (Olympus System Reagents 800, MIT Serice Inc.; San Diego CA).
- each of the enzyme solution A 100 ⁇ l each of the enzyme solution A are mixed with 900 ⁇ l of the dilutions of B or C.
- the activity of the enzyme is determined spectrophotometrically via its ability of degrading the slightly coloured p-nitrophenylphosphate to the intensely coloured p-nitrophenol (see Table 1). Defined inhibitory concentration [mg/l] Alk.
- phosphatase activity [units] phosphonomethylated chitosan Reference [units] 4536 205 907.2 104 453.6 39 90.72 15.5 45.36 23 9.072 41.5 4.536 73.5 0.9072 302 0.4536 302.5 0.09072 381.5 blind 1 reference ⁇ 325.5
- This mouth wash is excellently suitable for prophylaxis against bacterial plaque.
- Example 4 Measurement of the adsorption and desorption of microorganisms
- S. mutans (ZIB6008); S. mitis (KL-stab.); S. anguinosus (ZIB6006) and S. sanguis (ZIB6010) are plated out anaerobically on BA plates and incubated. One colony each is allowed to grow to a density of about 0.5 OD 660 in Todd-Hewitt broth as stock solution.
- HA Macro-Prep Ceramic Hydroxylapatite, 80micron, of BioRad
- 50mg of hydroxylapatite pearls are washed once with 1 ml of sterile H 2 O and three times with 1 ml of absorption buffer sterilised by filtration (5mM KCL, 1mM CCl 2 ; 0.1mM MgCl 2 ; 1mM K 2 HPO 4 , pH 7.2) (cf. Berry & Siragusa (1997); Appl. Environ. Microbiol. 63 , 4069-4074).
- 2ml of the bacterial solution are centrifuged (10,000 rpm, 5 min) and washed twice with adsorption buffer and are then resuspended in 1ml of adsorption buffer containing different concentrations of test substance or no test substance.
- This solution is combined with the hydroxylapatite pearls suspended in 1 ml of adsorption buffer and incubated, with slight shaking, for 30 min at 37°C. After the HA pearls have sedimented, the supernatant is removed. The HA pearls are dissolved in 1.6 ml of 0.5 N HCl.
- the optical density (OD 660 ) of this solution is determined and is placed in relation to the control containing no test substance prepared for each dilution series (control: 100% adsorption).
- S. mutans (ZIB6008); S. mitis (KL-stab.); S. anguinosus (ZIB6006) and S. sanguis (ZIB6010) are plated out anaerobically on BA plates and incubated. One colony each is allowed to grow to a density of about 0.5 OD 660 in Todd-Hewitt broth as stock solution.
- hydroxylapatite pearls (HA: Macro-Prep Ceramic Hydroxylapatite, 80micron, of BioRad) are washed once with 1 ml of sterile H 2 O and three times with 1 ml of absorption buffer sterilised by filtration (5mM KCl, 1mM CCl 2 ; 0.1 mM MgCl 2 ; 1mM K 2 HPO 4 , pH 7.2) (cf. Berry & Siragusa (1997); Appl. Environ. Microbiol. 63 , 4069-4074).
- 2 ml of the bacterial solution are centrifuged (10,000 rpm, 5 min) and washed twice with adsorption buffer and are then resuspended in 1 ml of adsorption buffer.
- This solution is combined with the hydroxylapatite pearls suspended in 1ml of adsorption buffer and incubated, with slight shaking, for 30 min at 37°C. After the HA pearls have sedimented, the supernatant is removed. The HA pearls are washed once with adsorption buffer and are then incubated, with slight shaking, for 30 min at 37°C with 1ml of adsorption buffer containing different concentrations of the test substance.
- the optical density (OD 660 ) of this solution is determined and is placed in relation to the control containing no test substance prepared for each dilution series (control: 0% desorption).
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Birds (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Emergency Medicine (AREA)
- Cosmetics (AREA)
- Polysaccharides And Polysaccharide Derivatives (AREA)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP98965242A EP1041960B1 (en) | 1997-12-22 | 1998-12-09 | Use of polyanionic and polyanionically-derivatised natural polysaccharides for inhibiting alkaline phosphatase |
Applications Claiming Priority (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP97811012 | 1997-12-22 | ||
EP97811012 | 1997-12-22 | ||
EP98810616 | 1998-07-02 | ||
EP98810616 | 1998-07-02 | ||
EP98965242A EP1041960B1 (en) | 1997-12-22 | 1998-12-09 | Use of polyanionic and polyanionically-derivatised natural polysaccharides for inhibiting alkaline phosphatase |
PCT/EP1998/007999 WO1999032073A1 (en) | 1997-12-22 | 1998-12-09 | Use of polyanionic and polyanionically-derivatised natural polysaccharides for inhibiting alkaline phosphatase |
Publications (2)
Publication Number | Publication Date |
---|---|
EP1041960A1 EP1041960A1 (en) | 2000-10-11 |
EP1041960B1 true EP1041960B1 (en) | 2002-07-17 |
Family
ID=26148115
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP98965242A Expired - Lifetime EP1041960B1 (en) | 1997-12-22 | 1998-12-09 | Use of polyanionic and polyanionically-derivatised natural polysaccharides for inhibiting alkaline phosphatase |
Country Status (7)
Country | Link |
---|---|
US (1) | US6514950B1 (hu) |
EP (1) | EP1041960B1 (hu) |
JP (1) | JP4064627B2 (hu) |
CN (1) | CN1283100A (hu) |
AU (1) | AU2052699A (hu) |
DE (1) | DE69806638T2 (hu) |
WO (1) | WO1999032073A1 (hu) |
Families Citing this family (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE19911055A1 (de) * | 1999-03-12 | 2000-09-21 | Cognis Deutschland Gmbh | Verwendung von oberflächenaktiven Gemischen |
US20030207945A1 (en) | 2001-12-20 | 2003-11-06 | Harper David Scott | Non-halogenated phenyl substituted phenols, antimicrobial compositions containing the same, and methods of using the same |
WO2002050008A2 (en) | 2000-12-20 | 2002-06-27 | Warner-Lambert Company Llc | Non-halogenated phenoxy and/or benzyloxy phenols and antimicrobial compositions containing them |
US7619008B2 (en) * | 2004-11-12 | 2009-11-17 | Kimberly-Clark Worldwide, Inc. | Xylitol for treatment of vaginal infections |
US20060217443A1 (en) * | 2005-03-28 | 2006-09-28 | Kimberly-Clark Worldwide, Inc. | Method for preventing and/or treating vaginal and vulval infections |
US7786176B2 (en) * | 2005-07-29 | 2010-08-31 | Kimberly-Clark Worldwide, Inc. | Vaginal treatment composition containing xylitol |
CN102516413B (zh) * | 2011-12-09 | 2014-02-12 | 中国科学院海洋研究所 | 一种呋喃基α-氨基膦酸酯壳聚糖衍生物及其制备方法 |
US20150328250A1 (en) * | 2012-12-19 | 2015-11-19 | Hill's Pet Nutrition, Inc. | Animal Food Composition and Method |
CN107709510A (zh) * | 2015-06-10 | 2018-02-16 | 罗地亚经营管理公司 | 膦酸酯化的多糖和凝胶以及其制备方法 |
Family Cites Families (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4515722A (en) | 1982-03-30 | 1985-05-07 | Merck & Co., Inc. | Phosphatidyl inositol analogs useful as anti-inflammatory/analgesic agents |
US4512968A (en) | 1982-11-30 | 1985-04-23 | Lion Corporation | Oral compositions |
US4627977A (en) | 1985-09-13 | 1986-12-09 | Colgate-Palmolive Company | Anticalculus oral composition |
SE512333C2 (sv) | 1989-08-25 | 2000-02-28 | Colgate Palmolive Co | Antibakteriell oral komposition med plack- och tandstensbegränsande verkan |
US5094844A (en) * | 1990-12-20 | 1992-03-10 | Colgate-Palmolive Company | Anticalculus oral composition |
US5202111A (en) | 1991-05-09 | 1993-04-13 | Chesebrough-Pond's Usa Co., Division Of Conopco, Inc. | Phosphorylated polyhydroxy compounds for tartar control |
GB9403153D0 (en) | 1994-02-18 | 1994-04-06 | Ciba Geigy Ag | Cosmetic compositions |
SE518597C2 (sv) | 1994-05-04 | 2002-10-29 | Medicarb Ab | Användning av kitosan i kombination med en sulfaterad, negativt laddad polysackarid för framställning av en dentalt verksam munhygienkomposition för behandling av parodontit, plaques och/eller karies |
DE59504682D1 (de) | 1994-11-24 | 1999-02-11 | Ciba Geigy Ag | Phosphonomethylierte Chitosane |
EP0803243B1 (en) | 1996-04-24 | 2003-03-19 | Pfizer Inc. | Cyclodextrins and phenolic compounds in dental products |
US5869029A (en) | 1996-06-21 | 1999-02-09 | Hercules Incorporated | Dispersible water-soluble or water-swellable polymers and process for making toothpastes containing them |
-
1998
- 1998-12-09 US US09/581,876 patent/US6514950B1/en not_active Expired - Fee Related
- 1998-12-09 WO PCT/EP1998/007999 patent/WO1999032073A1/en active IP Right Grant
- 1998-12-09 AU AU20526/99A patent/AU2052699A/en not_active Abandoned
- 1998-12-09 CN CN98812506A patent/CN1283100A/zh active Pending
- 1998-12-09 DE DE69806638T patent/DE69806638T2/de not_active Expired - Fee Related
- 1998-12-09 EP EP98965242A patent/EP1041960B1/en not_active Expired - Lifetime
- 1998-12-09 JP JP2000525069A patent/JP4064627B2/ja not_active Expired - Fee Related
Also Published As
Publication number | Publication date |
---|---|
EP1041960A1 (en) | 2000-10-11 |
DE69806638T2 (de) | 2003-03-13 |
DE69806638D1 (de) | 2002-08-22 |
JP4064627B2 (ja) | 2008-03-19 |
AU2052699A (en) | 1999-07-12 |
JP2001526201A (ja) | 2001-12-18 |
WO1999032073A1 (en) | 1999-07-01 |
US6514950B1 (en) | 2003-02-04 |
CN1283100A (zh) | 2001-02-07 |
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